Putting the brakes on anticancer therapies: suppression of innate immune pathways by tumor-associated myeloid cells

Abstract

Accumulating evidence has revealed that immunogenic cell death triggered by particular chemotherapeutic agents plays a critical role in harnessing antitumor immunity to clinical responses. However, negative regulatory pathways exist which suppress the induction of effective immune responses by a broad spectrum of anticancer therapies including 'non-immunogenic' regimens. Tumor-associated myeloid cells are unique in that they are capable of manipulating responses to anticancer drugs by utilizing negative regulatory factors of innate immune pathways, including damage-associated molecule-mediated pattern recognition and tolerogenic phagocytosis. Further elucidation of the molecular mechanisms regulating innate immune responses of tumor-associated myeloid cells under cellular stress should enhance the development of new molecular targeting therapies for patients with treatment-refractory cancers.

Keywords: chemoresistant niche; danger-associated molecular patterns; immunogenic cell death; innate immune pathways; phagocytosis receptors; tumor-associated myeloid cells.